Synthesis and antioxidant properties of some N- and O-containing 2-isobornyl-6-methylphenol derivatives

Russian Chemical Bulletin - A series of 2-isobornyl-6-methylphenol derivatives bearing either hydroxymethyl, aminomethyl, or N-acetylaminomethyl group at the para-position with respect to the...     

Synthesis and binding ability of mono- and tetrasubstituted aminophosphonate Zn-tetraarylporphyrins towards N- and O-containing organic substrates

The 1,6-addition of mono- and tetra-amino 5,10,15,20-tetraphenylporphyrins with dimethyl-(3,5-di-tert-butyl-4-oxocyclohexa-2,5-dienylidenemethyl)phosphonate leads to the corresponding mono- and tetrasubstituted aminophosphonate porphyrin derivatives. The binding ability of their Zn(II)-complexes towards 1,4-diazabicyclo[2,2,2]octane, imidazole, 4-(1H-imidazole-1-yl)benzyl alcohol and 4-(1H-imidazole-1-ylmethyl)benzyl alcohol in toluene was investigated by spectrophotometric and ¹H NMR titration. It has been determined that the monosubstituted Zn-tetraarylporphyrin is involved in a two-point selective binding of 4-(1H-imidazole-1-ylmethyl)benzyl alcohol. Taking into account the fact that this binding is accompanied by a clear and easily identifiable response in the UV–vis spectra of the reaction mixture, this metalloporphyrin could be considered as a molecular optical sensing device for selected bidentate N- and O-containing substrates.     

Gold-catalyzed 1,2-/1,2-bis-acetoxy migration of 1,4-bis-propargyl acetates: a mechanistic study

The late transition metal catalyzed rearrangement of propargyl acetates offers an interesting platform for the development of synthetically useful transformations. We have recently shown that gold complexes can catalyze a highly selective tandem 1,2-/1,2-bis-acetoxy migration in 1,4-bis-propargyl acetates to form 2,3-bis-acetoxy-1,3-dienes. In this way, (1Z,3Z)- or (1Z,3E)- and (1E,3Z)-1,3-dienes could be obtained in a stereocontrolled manner depending on the electronic and steric features of the ancillary ligand bound to gold and the substituents at the propargylic positions. In this work, we report an experimental study on the scope of this transformation, plus a detailed theoretical examination of the reaction mechanism, which has revealed the key features responsible for the reaction stereoselectivity. Synthetic applications towards the one-pot synthesis of quinoxaline heterocycles and tandem Diels-Alder processes have also been devised.     

Regioselective reactions of N-(carboxyalkyl)- and N-(aminoethyl)ureas with glyoxal and 1,2-dioxo-1,2-diphenylethane

Regioselective reactions of N-(carboxyalkyl)ureas (ureido acids) and N-(aminoethyl)ureas with 1,2-dioxo-1,2-diphenylethane (benzyl) and glyoxal are studied in detail. The structure of the reactants affects the reaction regioselectivity. Acid-catalyzed reactions of glyoxal with 1-[2-(dimethylamino(acetylamino))ethyl]ureas and benzene with ureido acids result mainly in 2,6-di-substituted glycolurils. The structure of 2,6-di(methoxycarbonylethyl)glycoluril is unambiguously established by X-ray diffraction.     

Asymmetrized tris(hydroxymethyl)methane as a precursor of N- and O-containing 6-membered heterocycles through ring-closing metathesis

A novel synthetic application of asymmetrized tris(hydroxymethyl)methane (THYM), obtained in both enantiomeric forms in high e.e. via a chemoenzymatic procedure, is described. Starting from the common precursor , N- and O-containing 6-membered heterocycles have been prepared exploiting ring-closing metathesis as the key step. Possible elaborations of the double bond in and have been explored and, in the case of , conversion into the glycosidase inhibitor isofagomine has been achieved.     

Gold-catalyzed consecutive [1,2] alkyl migration-oxygen transfer reaction of 2-alkynyl-1-tetralones

Gold-catalyzed isomerization of 2-alkynyl-1-tetralones afforded the corresponding 2-naphthylmethyl ketones in good to high yields. For example, the reaction of 2-{4-(methoxyphenyl)methyl}-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)-one and 2-benzyl-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)-one in the presence of 5 mol % of (Ph₃P)AuCl and 5 mol % of AgOTf in THF at 50 °C gave 2-{1-(4-methoxyphenylmethyl)naphthalen-2-yl}-1-(4-methoxyphenyl)ethanone and 2-(1-benzylnaphthalen-2-yl)-1-phenylethanone in 85% and 96% yields, respectively. The present reaction proceeds through [1,2] alkyl migration followed by oxygen transfer.     

Gold-catalyzed heterocycle synthesis using homopropargylic ethers as latent electrophiles

[reaction: see text] Homopropargylic ethers with pendent nucleophiles, when subjected to Au catalysts in aqueous solvent, provide heterocyclic ketones. The reactions are efficient, tolerant of functionality and ambient atmosphere, and operationally simple. Diastereoselectivity can be predicted on the basis of product thermodynamics. This process demonstrates the viability of homopropargylic ethers to serve as latent electrophiles that can be unraveled under highly selective conditions to promote heterocycle formation through nucleophilic additions to alpha,beta-unsaturated ketones.     

Gold-catalyzed tandem C-C and C-O bond formation: a highly diastereoselective formation of cyclohex-4-ene-1,2-diol derivatives

We have reported an efficient gold(I)-catalyzed tandem cyclization of tert-butyl carbonate derivatives of hex-1-en-5-yn-3-ol where nucleophilic participation of the O-Boc group appears to intercept a carbocationic (or cyclopropyl carbene) Au intermediate. This novel protocol leads to densely functionalized cyclohexene-3,4-diol derivatives where 1,2- or 1,2,3-stereocenters are controlled in a highly diastereoselective fashion.     

Gold-catalyzed 1,2-migration of silicon, tin, and germanium en route to C-2 substituted fused pyrrole-containing heterocycles

An efficient method for the synthesis of fused pyrroloheterocycles from diverse propargyl-substituted heterocycles in the presence of Au-catalyst has been developed. The cascade transformation proceeds via alkyne-vinylidene isomerization with concomitant 1,2-shift of hydrogen, silyl, and stannyl groups. Remarkably, it was also shown that previously unknown 1,2-migration of a germyl group upon alkyne-vinylidene rearrangement occurs under these reaction conditions. This method allows for mild and efficient synthesis of diverse C-2 substituted N-containing heterocycles.     

Synthesis of regioisomeric N- and O-alkylated 3-polyfluoroalkyl-1,2-dihydroquinoxalin-2-ones

3-Polyfluoroalkyl-1,2-dihydroquinoxalin-2-ones react with 4-bromobutyl acetate to furnish 1-(4-acetoxybutyl)quinoxalin-2-ones and 2-(4-acetoxybutoxy)quinoxalines in the ratio 2: 1. Deacylation of these compounds under acidic conditions gives the corresponding 1-(4-hydroxybutyl)- and 2-(4-hydroxybutoxy)-substituted quinoxalines. The structures of compounds synthesized were established by X-ray crystallography, IR spectroscopy, ¹H and ¹⁹F NMR spectroscopy, GLC-MS.     

Synthesis and transformations of metallacycles 41. Cyclomagnesiation of O-containing 1,2-dienes with Grignard reagents in the presence of Cp2TiCl2

A Cp₂TiCl₂-catalyzed intermolecular homocyclomagnesiation of O-containing 1,2-dienes and cross-cyclomagnesiation of O-containing 1,2-dienes with aliphatic 1,2-dienes of cyclic and acyclic structure have been accomplished using Grignard reagents, which led to mono- and bicyclic organomagnesium compounds in 61–94% yields.     

1,2-oxazine chemistry—II : The crystal and molecular structure of N-(p-carboxybenzyl)-tetrahydro-1,2-oxazine

The crystal structure of the title compound has been determined from X-ray diffractometer data by direct methods, and refined by full matrix least squares techniques to R = 0·057 for 1231 reflections. The crystals are monoclinic, space group C2/C, cell dimensions a = 1665, b = 987, c = 1443 pm, β = 107·37° and Z = 8. The conformation of the tetrahydro-1,2-oxazine ring is a chair with the N-substituent equatorial. There is evidence of significantly greater torsional angles around the N and O atoms than around the ring C atoms, showing the ring to be more puckered than cyclohexane. The hydrogen bond is between the acid group on one molecule and the ring nitrogen on its neighbour.     

Gold-catalyzed assembly of heterobicyclic systems

We have described an efficient gold-catalyzed double cyclization of 1,5-enynes to afford a range of heterobicyclic compounds, including oxabicylclo[3.2.1]octenes, azabicyclo[3.2.1]octenes, oxaspiro[5.4]decene, azaspiro[5.4]decene, oxaspiro[5.5]undecene, oxabicyclo[4.3.0]nonene, azabicyclo[4.3.0]nonene, and oxabicyclo[4.4.0]decene. The mechanism of this reaction is proposed to involve a chemoselective gold-based alkyne activation, carbocyclization, intramolecular nucleophilic addition, followed by protodemetalation. The most notable aspect of this process is the efficient and diastereospecific interception of the reactive intermediate of the initial 6-endo-dig (or 5-endo-dig) cyclization with either oxygen- or nitrogen-based nucleophiles.     

Gold-catalyzed synthesis of substituted tetrahydronaphthalenes

We report a gold-catalyzed benzannulation of 3-hydroxy-1,5-enynes to generate tetrahydronaphthalenes. This mild process proves to be an effective method to synthesize various metasubstituted aromatic rings in good yields. [reaction: see text]     

Gold-catalyzed and N-iodosuccinimide-mediated cyclization of gamma-substituted allenamides

Chiral gamma-substituted allenamides have been shown to undergo efficient gold-catalyzed and N-iodosuccinimide-mediated cyclization to highly functionalized dihydrofurans. These reactions proceed rapidly and without loss of stereochemistry.     

Gold-catalyzed tandem cycloisomerization-hydroalkoxylation of homopropargylic alcohols

The tandem cycloisomerization-hydroalkoxylation of various homopropargylic alcohols in the presence of an alcohol and a dual catalyst system, consisting of a gold precatalyst and a Br?nsted acid, provides an efficient route to tetrahydrofuranyl ethers under mild reaction conditions. The reaction can be carried out in various solvents, including alcohol, with both terminal and internal alkynes as the substrate.